This is a proposal to conduct a case-control study to test the hypothesis that infection with human papilloma virus (HPV) and/or herpes simplex virus (HSV) is related to an increased risk of oral cancer. The study will be conducted in three counties of western Washington that are covered by the population-based Cancer Surveillance System (CSS), a tumor registry that participates in the Surveillance Epidemiology and End Results Program (SEER) of the National Cancer Institute. All men and women aged 18-65 diagnosed with squamous cell carcinoma of the tongue, gum, floor of the mouth, other and unspecified parts of the mouth, and oropharynx will be identified and invited to participate. Eligible subjects will be all incident cases (180 men, 120 women) from July 1988 to June 1994. General population controls will be frequency matched to cases on age, sex, and geographic location will be selected by random digit dialing. Cases and controls will be interviewed regarding a history of sexually transmitted diseases, sexual practices, as well as other known or suspected risk factors for oral cancer. Tissue specimens and exfoliated oral cavity cells will be collected from each case. A biopsy specimen will be obtained from a segment of the interviewed controls, and exfoliated oral cavity cells will be obtained from all controls. These tissue samples will be examined using molecular hybridization techniques. Blood samples will be collected for all cases and controls and analyzed for evidence of prior exposure to sexually transmitted diseases. A sample of blood will be stored for analysis when a test for HPV becomes available.